Resident Skin-specific γδ T Cells Provide Local, Nonredundant Regulation of Cutaneous Inflammation

Abstract

The function of the intraepithelial lymphocyte (IEL) network of T cell receptor (TCR) γδ+ (Vγ5+) dendritic epidermal T cells (DETC) was evaluated by examining several mouse strains genetically deficient in γδ T cells (δ−/− mice), and in δ−/− mice reconstituted with DETC or with different γδ cell subpopulations. NOD.δ−/− and FVB.δ−/− mice spontaneously developed localized, chronic dermatitis, whereas interestingly, the commonly used C57BL/6.δ−/− strain did not. Genetic analyses indicated a single autosomal recessive gene controlled the dermatitis susceptibility of NOD.δ−/− mice. Furthermore, allergic and irritant contact dermatitis reactions were exaggerated in FVB.δ−/−, but not in C57BL/6.δ−/− mice. Neither spontaneous nor augmented irritant dermatitis was observed in FVB.β−/− δ−/− mice lacking all T cells, indicating that αβ T cell–mediated inflammation is the target for γδ-mediated down-regulation. Reconstitution studies demonstrated that both spontaneous and augmented irritant dermatitis in FVB.δ−/− mice were down-regulated by Vγ5+ DETC, but not by epidermal T cells expressing other γδ TCRs. This study demonstrates that functional impairment at an epithelial interface can be specifically attributed to absence of the local TCR-γδ+ IEL subset and suggests that systemic inflammatory reactions may more generally be subject to substantial regulation by local IELs.

γδ T Cells Are Necessary for Platelet and Neutrophil Accumulation in Limbal Vessels and Efficient Epithelial Repair after Corneal Abrasion

“…There is convincing evidence that the ␥␦ T cells in the skin, also called dendritic epidermal T cells, play a critical role in wound healing 15,41 and in the maintenance of epidermal integrity. 35,42,43 Dendritic epidermal T cells apparently recognize endogenous factors released or expressed on stressed or damaged epidermal cells 42,44 and are activated through ligation of the TCR. Activation may result in release of proinflammatory chemokines such as XCL1, CXCL1, CCL3, CCL4, and CCL5 45 that are capable of attracting other leukocytes and releasing growth factors such as FGF-7 and FGF-10 41 that influence the division and migration of keratinocytes.…”

Antibodies to wounded tissue enhance cutaneous wound healing

“…[2][3][4][5][6][7][8] In contrast, there are few reports that describe the effects of T or B cells in wound healing except cd T cells. 9,10 In aseptic wound healing, very few T or B cells migrate to the wound site. However, immunoglobulin secreted by B cells can reach wound sites.…”

RSV bronchiolitis, γδ T cells and asthma: are they linked?

“…They seem to have a protective role against intracellular microbial infections, particularly mycobacteria and protozoa. More controversially, they may also protect against cutaneous carcinomas [4] and perhaps suppress ab T cell-mediated inflammation in allergic states [5].In this issue of Clinical and Experimental Immunology , Aoyagi et al . report a study of 15 infants with severe lung infections due to respiratory syncytial virus (RSV) and seven with reovirus infections of the gut.…”

“…They seem to have a protective role against intracellular microbial infections, particularly mycobacteria and protozoa. More controversially, they may also protect against cutaneous carcinomas [4] and perhaps suppress ab T cell-mediated inflammation in allergic states [5].…”